Triarylphosphonium-conjugated Sn(iv)-porphyrins for antimicrobial photodynamic therapy: impact of substituents on lipophilicity, aggregation, and photoantibacterial activity

Abstract

Antimicrobial photodynamic therapy is an effective approach to counteract bacterial infections that are not possible to be treated through antibiotics. In this study, three cationic Sn(IV) porphyrins bearing triaryl phosphonium substituents (SnP1, SnP2, and SnP3) were synthesized and evaluated as antibacterial photosensitizers (PSs). All compounds exhibited efficient singlet oxygen generation with quantum yields (Φ_Δ) in the range of 0.72–0.78. Aggregation studies show reduced aggregation of SnP1 and SnP2 than SnP3. Lipophilicity (log P) values indicated that SnP2, containing fluoro substituents, possesses a balanced amphiphilic character favorable for effective bacterial uptake and antimicrobial activity. The photodynamic antibacterial activity (427 nm LED; 22 mW cm⁻²) of SnP1, SnP2 and SnP3 was evaluated against Escherichia coli (E. coli) and clinical methicillin-resistant Staphylococcus aureus (MRSA). SnP2 exhibited significant photoantimicrobial activity against both Gram-negative (E. coli) and Gram-positive (MRSA) bacteria with a log reduction of 8.7 at 10 μM and 8.5 at 20 nM, respectively. Overall, our study highlights the importance of structural tuning of lipophilicity and aggregation in enhancing the efficacy of Sn(IV)-porphyrin-based photosensitizers.